The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells.
The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells.
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microRNA miR-34a 抑制非小细胞肺癌 (NSCLC) 生长和 CD44hi 干细胞样 NSCLC 细胞
DOI：
10.1371/journal.pone.0090022
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Shi Y;Liu C;Liu X;Tang DG;Wang J
肺癌是最致命的恶性肿瘤之一，具有较高的转移率和复发率，这可能与肺癌干细胞的存在有关。黏附分子CD44单独或与其他标记物(S)联合应用，已在包括非小细胞肺癌在内的许多肿瘤中鉴定出CSCs。MicroRNAs(MiRNAs)调节正常干细胞和CSCs，miRNAs的失调与肿瘤的发生有关。最近发现miR-34a在NSCLC细胞中表达下调，但miR-34a在调控NSCLC细胞行为中的生物学功能尚未得到广泛研究。在这里，我们发现，在A549、H460和H1299这三个非小细胞肺癌细胞系中，转导合成的miR-34a，而不是阴性对照(NC)miRNA寡核苷酸，可以抑制它们的全克隆形成、克隆形成和体内肿瘤的再生。此外，慢病毒载体介导的miR-34a在纯化的CD44hi H460细胞中的过表达也抑制了肿瘤的生长。相反，在CD44lo H460细胞中表达miR-34a反义寡核苷酸促进了肿瘤的发展。我们的研究表明，miR-34a是非小细胞肺癌细胞和CD44hi肺肿瘤干细胞的致瘤负性调节因子，为开发miR-34a作为治疗非小细胞肺癌的新药物奠定了坚实的基础。
Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate, which is probably due to the existence of lung cancer stem cells (CSCs). CSCs in many tumors including non-small cell lung cancer (NSCLC) have been identified using adhesion molecular CD44, either individually or in combination with other marker(s). MicroRNAs (miRNAs) regulate both normal stem cells and CSCs and dysregulation of miRNAs has been implicated in tumorigenesis. Recently, miR-34a was found to be downregulated in NSCLC cells but the biological functions of miR-34a in regulating NSCLC cell behavior have not been extensively studied. Here we show that transfection of synthetic miR-34a, but not the negative control (NC) miRNA oligonucleotides (oligos) in three NSCLC cell lines, i.e., A549, H460, and H1299, inhibited their holoclone formation, clonogenic expansion, and tumor regeneration in vivo. Furthermore, the lentiviral vector-mediated overexpression of miR-34a in purified CD44hi H460 cells also inhibited tumor outgrowth. In contrast, expression of miR-34a antagomirs (i.e., antisense oligos) in the CD44lo H460 cells promoted tumor development. Our study shows that miR-34a is a negative regulator of the tumorigenic properties of NSCLC cells and CD44hi lung CSCs, and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against NSCLC.
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影响因子：
5.2
作者：
Das, Bikul;Tsuchida, Rika;Yeger, Herman
通讯作者：
Yeger, Herman
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
MiR-34a通过下调Bcl-2和SIRT1抑制乳腺癌的增殖和迁移
影响因子：
4.6
作者：
Li, Laisheng;Yuan, Linjin;Xie, Xiaoming
通讯作者：
Xie, Xiaoming
表达 CD44 的非小细胞肺癌细胞富含干细胞样特性。
影响因子：
3.7
作者：
Leung, Elaine Lai-Han;Fiscus, Ronald R.;Tung, James W.;Tin, Vicky Pui-Chi;Cheng, Lik Cheung;Sihoe, Alan Dart-Loon;Fink, Louis M.;Ma, Yupo;Wong, Maria Pik
通讯作者：
Wong, Maria Pik
影响因子：
3.6
作者：
Chen, Fei;Hu, Shen-Jiang
通讯作者：
Hu, Shen-Jiang